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Zoledronic acid (ZA), a widely used bisphosphonate, is associated with acute phase reaction (APR) that may trigger adrenal crisis in susceptible individuals. We describe two patients with hypopituitarism and osteoporosis who developed adrenal crisis shortly after their first ZA infusion, despite stable physiological steroid replacement and acetaminophen prophylaxis. One presented with hypotension and shock within 24\u2009h, the other with hypotension, severe hyponatremia, and seizures at 48\u2009h. Both recovered after high\u2010dose glucocorticoids and were later switched to denosumab without complications. These cases highlight the potential for adrenal crisis in patients with central AI receiving ZA and suggest that standard prophylaxis may be insufficient. Alternative therapies and enhanced precautions may be warranted in this vulnerable population.<\/jats:p>","DOI":"10.1155\/crie\/8854575","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:29:25Z","timestamp":1767860965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adrenal Crisis Induced by Zoledronic Acid in Two Patients With Hypopituitarism: A Case Report and Literature Review"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-7113","authenticated-orcid":false,"given":"Abrar Mohammed","family":"AlFaifi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6701-5252","authenticated-orcid":false,"given":"Wael Mohammad","family":"AlMistehi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61684-0"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2010.03188.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S149069"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-024-01391-2"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1370240"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-025-07574-2"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-012-0041-1"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60752-0"},{"key":"e_1_2_10_9_2","first-page":"88","article-title":"Adrenal Crisis After Zoledronic Acid Infusion in a Patient of Sheehan Syndrome: A Case Report and Review of Literature","volume":"1","author":"Basu R.","year":"2023","journal-title":"IJEM Case Reports"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aace.2022.12.003"},{"key":"e_1_2_10_11_2","doi-asserted-by":"crossref","unstructured":"SmrecnikM. Kavcic TrsinarZ. andKocjanT. Adrenal Crisis After First Infusion of Zoledronic Acid: A Case Report. Osteoporosis International: A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2018 29 no. 7 1675\u20131678 https:\/\/doi.org\/10.1007\/s00198-018-4508-7 2-s2.0-85044473272.","DOI":"10.1007\/s00198-018-4508-7"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.1022"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.521"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.4158\/EP161638.OR"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12865"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.4802"},{"key":"e_1_2_10_17_2","doi-asserted-by":"crossref","unstructured":"SilvermanS. L. KriegmanA. GoncalvesJ. KianifardF. CarlsonT. andLearyE. Effect of Acetaminophen and Fluvastatin on Post-Dose Symptoms Following Infusion of Zoledronic Acid. Osteoporosis International: A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2011 22 no. 8 2337\u20132345 https:\/\/doi.org\/10.1007\/s00198-010-1448-2 2-s2.0-79960216013.","DOI":"10.1007\/s00198-010-1448-2"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-011-1563-8"},{"key":"e_1_2_10_19_2","doi-asserted-by":"crossref","unstructured":"ChenF. P. FuT. S. LinY. C. andLinY. J. Addition of Dexamethasone to Manage Acute Phase Responses Following Initial Zoledronic Acid Infusion. 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